Synthesis of novel fluorinated flavonols via Algar-Flynn-Oyamada reaction

Abstract

Flavonols have attracted considerable attention due to their diverse biological effects. However, naturally occurring flavonols are typically present only in low concentrations, with fluorine-containing flavonols being especially rare. In that respect, the construction of diverse flavonol analogues is attractive to synthetic chemists. As part of our efforts to develop fluorinated flavonols, a series of fifteen fluorinated flavonols (1-15) were synthesised via the oxidative cyclisation of 2′-hydroxychalcones with hydrogen peroxide in an alkaline ethanol solution, using the Algar-Flynn-Oyamada (AFO) reaction. Despite the relative simplicity and convenience of the AFO reaction, the isolated yields of the fluoro-substituted flavonols were relatively modest, ranging from 16 to 51%. The cyclisation yields of flavonols were found to be favourable in the presence of fluorine substituents at the 2′- or 3′-position in the B ring. The structures of the fluorinated flavonols were elucidated by nuclear magnetic resonance (NMR) and mass spectrometry (MS) data. It is of interest to note that this work, for the first time, demonstrates the synthesis of six novel fluorinated flavonols (7, 8, 12-15) through the application of the AFO approach.